CATEGORY: IMMUNE DYSFUNCTION ANAPHYLAXIS

Anaphylaxis
Tariq El-Shanawany, University Hospital of Wales, UK

Anaphylaxis is a severe, life-threatening, generalised or systemic hypersensitivity reaction, with

significant disturbance of one or more of airway, breathing or circulation. It is not clear why one
person with specific immunoglobulin E (IgE) to an allergen will have an anaphylactic reaction on
exposure, another only a local reaction, and in a third individual no reaction at all. Some risk factors

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have been defined, such as low levels of platelet activating factor acetylhydrolase and low levels of
serum angiotensin converting enzyme, both of which independently increase the risk of an allergic
individual developing anaphylaxis on allergen exposure. Local and systemic allergic reactions occur
via similar mechanisms that differ in location and magnitude. It should be noted that fatal allergic
reactions can occur without anaphylaxis being present. For example, angioedema affecting the upper
airway may be a lethal local reaction and other reactions may kill by inhalation of vomit. Some
medicines such as non steroidal anti-inflammatory drugs (NSIADS) can worsen allergic reactions
including anaphylaxis.
Anaphylaxis results from the actions of a wide range of mediators released by mast cell and
basophil degranulation (Table 1). Many of these mediators are preformed and stored in the
granules, whereas others are produced de novo on activation of mast cells and basophils.
Degranulation can be mediated by cross-linking of IgE bound to membrane high-affinity IgE
receptor (FcRI), or by non-IgE-mediated mechanisms. The distinction between these mechanisms
can be important diagnostically, but their clinical presentation and the medical management of the
acute emergency they cause are indistinct.
The clinical presentation of anaphylaxis
is variable and many different organ Type Example(s) Effect
systems may be affected. The skin may Enzymes Tryptase, chymase Remodel connective tissue matrix
itch (pruritus) with or without weals
(urticaria) and/or swelling (angioedema). Toxic Mediators Histamine, heparin Toxic Vascular permeability
to parasites

There may be nausea, abdominal pain, Smooth muscle contraction

vomiting and/or diarrhoea. Swelling may Cytokines IL-4, IL-13 TH2 response
involve the lip, tongue, throat and/or IL-3, IL-5, GM-CSF Eosinophil production & activation
upper airway impairing swallowing TNF- Inflammation
(dysphagia), speech (dysphonia) or Chemokines CCL3 Monocyte, macrophage &
breathing (with stridor and/or neutrophil chemotaxis

Vascular permeability
asphyxiation). The lungs can be affected Lipid mediators Leukotrienes C4, D4, Smooth muscle contraction
E4
with cough, wheeze and bronchospasm Mucus secretion
with a corresponding fall in the peak
production of lipid mediators
Platelet activating Chemotaxis
expiratory flow rate. Cardiovascular factor
events include chest pain, hypotension
Table 1. Examples of mediators released during
and fainting (syncope). anaphylaxis
The emergency treatment of anaphylaxis involves the prompt administration of adrenaline. Other
treatments such as anti-histamines, intravenous fluids and steroids are also commonly used, but
should not lead to a delay in the administration of adrenaline. Adrenaline autoinjectors are commonly
prescribed to patients at high risk of anaphylaxis, so that they are able to self-administer adrenaline in
an emergency (Figure 1). After surviving an episode of anaphylaxis, it is important that the patient is
referred to an Immunology or allergy clinic to identify the cause, and thereby reduce the risk of future
reactions and prepare the patient to manage future episodes.

Figure 1. An example of an adrenaline autoinjector